Microglial interactions with the Perineuronal Net
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Principal Investigator: JOSHUA Craig BRUMBERG Organization: QUEENS COLLEGE Fiscal Year: 2024 Award: $115,500 Funding agency: National Institute of General Medical Sciences Abstract Sensory Deprivation profoundly impacts cortical circuits which in turn impact organismal functioning from mouse to man. Traditionally research has focused on how neurons respond to changes in sensory experience during development. Recently attention has been drawn to non- neuronal elements such as microglia and the perineuronal net (neuron specific form of the extracellular matrix). Microglia, the brains immune cells, alter their morphology in response to whisker trimming evoked sensory deprivation, their somata enlarge and their process retract, hallmarks of their activated state. Coincident with this, the perineuronal net is reduced preferentially around parvalbumin positive GABAergic interneurons. Physiological studies have shown that these neurons play a key role in regulating cortical excitability and following perineuronal net digestion we found their intrinsic physiological properties become altered (lower probability of spiking, lower input resistance). Our overarching hypothesis is that sensory deprivation activates microglia which in turn shape the perineuronal net. We will investigate this causal relationship by depleting microglia while trimming the animal’s whiskers and evaluating the perineuronal net. The functional consequences of this relationship will be studied using whole-cell patch clamp recordings in the thalamocortical slice and finally the behavioral ramifications will be assayed using a texture based novel object paradigm. Terms: <21+ years old><Abscission><Acute><Adopted><Adult><Adult Human><Anatomic Sites><Anatomic structures><Anatomy><Animals><Assay><Attention><Behavior><Behavioral><Bioassay><Biological Assay><Brain><Brain Nervous System><CSF-1><Cell Body><Cell Protection><Cell-Extracellular Matrix><Cells><Characteristics><Colony-Stimulating Factor 1><Communication><Connector Neuron><Coupled><Cytoprotection><Development><Digestion><Dysfunction><ECM><EPSP><Elements><Encephalon><Environment><Excision><Excitatory Postsynaptic Potentials><Extirpation><Extracellular Matrix><Frequencies><Functional disorder><Glia><Glial Cells><Hortega cell><Image Analyses><Image Analysis><Immune><Immunes><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Inflammatory Response><Injections><Intercalary Neuron><Intercalated Neurons><Interneurons><Internuncial Cell><Internuncial Neuron><Kinetics><Kolliker's reticulum><Lipopolysaccharides><M-CSF><Macrophage Colony-Stimulating Factor><Mice><Mice Mammals><Microglia><Minocycline><Morphology><Murine><Mus><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neuroglia><Neuroglial Cells><Neurologic Disorders><Neurological Disorders><Neurons><Non-neuronal cell><Nonneuronal cell><Organism><Parvalbumins><Performance><Physiologic><Physiological><Physiopathology><Play><Probability><Process><Property><Public Health><Removal><Research><Resistance><Role><Sensory><Sensory Deprivation><Shapes><Slice><Somatosensory Cortex><Stress><Structure><Surgical Removal><Synapses><Synaptic><Texture><Thalamic structure><Thalamus><Training><Vibrissae><Whiskers><Work><adulthood><cytoprotective><density><developmental><discrimination task><experience><experiment><experimental research><experimental study><experiments><gitter cell><image evaluation><image interpretation><inhibitor><living system><man><mesoglia><microglial cell><microgliocyte><mouse development><nerve cement><neural><neural circuit><neural circuitry><neurocircuitry><neurological disease><neurological pathology><neuronal><novel><oxidation><patch clamp><pathophysiology><perivascular glial cell><pharmacologic><preservation><receptive field><resection><resistant><response><sensory input><social role><somesthetic sensory cortex><synapse><synaptic circuit><synaptic circuitry><thalamic><whisker based discrimination><whisker dependent discrimination><whisker discrimination>